Supplementary Fig. S1 DAY 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 33 35 36 p2 p3 p4 p5 p6 p7 p8 p9 p10 p11 p12 p13a p14 p15 p16 p17 p18b p19 p20 p21b p22 p23 p24 p25 p26 p27 p28b p29 p30 p31 p32 p33 p34b p35 p36

SARS-CoV-2 positive SARS-CoV-2 positive Throat swabs Anal swabs Hospitalization SARS-CoV-2 negative SARS-CoV-2 negative Supplementary Fig. S2

p36 Indicator (Genus) p35 p34 Ⅰ

p33 |Alloprevotella p32 p31 Ⅱ p30 Bacteroidetes|Bacteroidales*

p29 Bacteroidetes|Porphyromonas p28 Fusobacteria| p27 |Neisseria p26 p25 Ⅲ p24 Proteobacteria|Pseudomonas p23 p22 Ⅳ p21

p20 |*

p19 Actinobacteria|Rothia p18 Candidatus |

COVID -19 P atients Saccharibacteria p17 * unclassified genera p16

p15

p14 p13

p12

p11

p10

p09

p08 p07 p06 p05 p04 p03

p02 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 Days after symptom onset Supplementary Fig. S3

p36

p35

p33 Indicator (Genus) p32 Ⅰ p29 Bacteroidetes|Bacteroides p27 Bacteroidetes|Parabacteroides p25 |Anaerostipes

p23 Firmicutes|Blautia Firmicutes|Coprococcus p20 Firmicutes|Dorea p17 Firmicutes|

COVID -19 P atients p15 Firmicutes|Finegoldia

p13 Firmicutes|Fusicatenibacter Firmicutes|Lachnospiraceae* p11 Firmicutes|Roseburia p08 p07 Ⅱ p06 Proteobacteria|Neisseria p05 Ⅲ

p04 Proteobacteria|Pseudomonas p03 * unclassified genera 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 Days after symptom onset Supplementary Fig. S4

a Female Male b 17−33 years old 39−59 years old >63 years old

1.00 0.8 4 PFDR = 2.65e-02 8 0.75 13 0.6 4 10 7 4 ercent ercent 27 23 0.50 0.4 2

17 2 2 actor P actor P 0.25 0.2 4 3 10 11 1 1 F F 2 3 2 0.00 0.0 A(N = 16) B(N = 44) C(N = 10) D(N = 4) NP(N = 6) A(N = 16) B(N = 44) C(N = 10) D(N = 4) NP(N = 6) c d Virus detection Negative Positive Antibiotic Uses No Yes

12 3 3 11 0.6 29 0.6 4 3 5 23 5 5 ercent ercent 0.4 4 0.4 21 15 2 5 2 0.2 4 1 0.2 1 actor P actor P F F

0.0 0.0 A(N = 16) B(N = 44) C(N = 10) D(N = 4) NP(N = 5) A(N = 16) B(N = 44) C(N = 10) D(N = 4) NP(N = 6) Supplementary Fig. S5 a b Female Male 17−33 years old 39−59 years old >63 years old

0.8 1.00 12 6 0.6 16 4 0.75

ercent 0.4 0.50 9 8 2 11 0.2 0.25 8 actor P 3 4 F Factor Percent 5 2 0.0 0.00 A(N = 15) B(N = 24) C(N = 6) A(N = 15) B(N = 24) C(N = 6) c d Virus detection Negative Positive Antibiotic Uses No Yes

0.8 12 13 22 19 0.75 5 0.6 4

ercent 0.50 0.4 2 0.25

actor P 0.2 F Factor Percent 3 5 2 1 0.00 2 0.0 A(N = 15) B(N = 24) C (N = 6) A(N = 15) B(N = 24) C(N = 6) Supplementary Fig. S6

Throat indicator Gut indicator Ⅰ Haemophilus Parasutterella Alloprevotella Ruminococcus Ruminococcaceae* Roseburia Peptoniphilus Lachnospiracea Lachnospiracea incertae sedis Fusicatenibacter Finegoldia Faecalibacterium Ⅰ Dorea Coprococcus Blautia Anaerostipes Parabacteroides Bacteroides

Porphyromonas * Neisseria Ⅱ Neisseria Fusobacterium Leptotrichiaceae* Bacteroidales* Leptotrichia Fusobacterium Ⅱ Oribacterium Lactobacillales* Lachnoanaerobaculum Gemella Porphyromonas Capnocytophaga

Ⅲ Pseudomonas Pseudomonas Ⅲ

Saccharibacteria *Unclassfied genera Ⅳ incertae sedis Rothia Actinomycetales* Supplementary Fig. S7 SARS-CoV-2

Respiratory tract

Epithelial Cells Faecalibacterlum Bacteroidales Prevotella Saccharibacteria sedis Comamonadaceae Bifidobacterium Fusobacterium Neisseria Pseudomonas Bacteroides Alloprevotella Porphyromonas Rothia s Ax i

t High diversity u G -

y Ⅰ Ⅱ Ⅲ/Ⅳ a w

r Low diversity A i (Dysbiosis)

Normal gut dominant butyrate-producing Resident microbiome Roseburia Faecalibacterlum Blautia Neisseria Pseudomonas Lachnospiraceae Coprococcus Bifidobacterium Bacteroides ……

ACE2

Epithelial Cells Gut

Healthy COVID-19 Days a�er symptom onset